Inflammation in cardiovascular disease: cart, horse, or both?

In this issue of Circulation , Ridker and colleagues1 discuss the incremental value of CRP as a predictor of future CVD events. Their conclusion is that CRP is at least additive to HDL and total cholesterol with respect to risk prediction. In fact, there is some evidence that lipids and CRP are better predictors jointly than would be expected by adding up their individual predictive powers. CRP appeared to predict events in those at low risk on the basis of lipids, and CRP-lipid relationships to events were minimally altered by adjustment for other known CVD risk factors. These findings have important implications for CVD risk assessment and risk management. CRP is an acute-phase reactant, the levels of which increase dramatically (100-fold or more) in response to severe bacterial infection, physical trauma, and other inflammatory conditions.2 Several roles have been postulated for CRP, including that of an opsonin, promoting the phagocytic uptake of invading microorganisms, and that of a procoagulant, promoting the expression of tissue factor on the monocyte surface. As a marker of inflammation, CRP is unique among the major plasma proteins in the fold increase that is observed and in that its levels appear to be unaffected by hormones and anti-inflammatory drugs but are regulated primarily by the proinflammatory cytokines, especially IL-6.2 3 Traditionally, 10 mg/L has been used as the cut point to signify clinically important levels, with values in the healthy reference range at or below the lower limit of sensitivity of most assays. Recently, elevated levels of CRP, although still for the most part in the healthy reference range, have been associated with increased risk of future CVD events. Initially, Liuzzo et al4 and Haverkate et al5 established the prognostic usefulness of CRP in the setting of angina. This was followed …